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Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs., Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6-65) was divided into six successive 6-10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients., Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6-13 and adults aged 50-65 with OCD taking SRIs (Cohen's d = -0.24 to -0.74). Volumes of putamen, pallidum (d = 0.18-0.40), and ventricles (d = 0.31-0.66) were greater in patients aged 20-29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = -0.27 to -1.31)., Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20-29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response., Competing Interests: Conflict of Interest Dr. Arnold reported holding the Alberta Innovates Translational Health Chair in Child and Youth Mental Health outside the submitted work. Prof. Mataix-Cols receives royalties for contributing articles to UpToDate, Wolters Kluwer Health and fees from Elsevier for editorial tasks (all unrelated to the submitted work). Dr. Narayanaswamy reported Government of India grants DST INSPIRE faculty grant IFA12-LSBM-26 and BT/06/IYBA/2012 outside the submitted work. Dr. Reddy reported Government of India grants SR/S0/HS/0016/2011 and BT/PR13334/Med/30/259/2009 outside the submitted work. Dr. Venkatasubramanian reported Wellcome-DBT India Alliance grant 500236/Z/11/Z outside the submitted work. Dr. Simpson reported Biohaven Research support for a clinical trial and royalties from UpToDate, Inc. and Cambridge University Press outside the submitted work. Dr. Soreni reported support from Lundbeck-IIT outside the submitted work. Dr. Walitza has received in the last 3 years royalties from Thieme Hogrefe, Kohlhammer, Springer, Beltz; Her work was supported in the last 3 years by the Swiss National Science Foundation (SNF), diff. EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, Gertrud Thalmann Fonds (all unrelated to the submitted work). Dr. Thompson has received a research grant from Biogen, Inc., unrelated to the topic of this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Distortions in time processing may be regarded as an endophenotypic marker of neuropsychiatric diseases; however, investigations addressing Bipolar Disorder (BD) are still scarce., Methods: The present study compared timing abilities in 30 BD patients and 30 healthy controls (HC), and explored the relationship between time processing and affective-cognitive symptoms in BD, with the aim to determine whether timing difficulties are primary in bipolar patients or due to comorbid cognitive impairment. Four tasks measuring external timing were administered: a temporal and spatial orienting of attention task and a temporal and colour discrimination task, for assessing the ability to evaluate temporal properties of external events; two other tasks assessed the speed of the internal clock (i.e. temporal bisection and temporal production tasks). Attentional, executive and working memory (WM) demands were equated for controlling additional cognitive processes., Results: BD patients did not show differences in external timing accuracy compared to HC; conversely, we found increased variability of the internal clock in BD and this performance was related to Major Depressive Episodes recurrence and WM functioning. Hence, variability of the internal clock is influenced by the progressive course of BD and impacted by variations in WM., Limitations: Future studies including BD patients stratified by mood episode will further specify timing alterations conditional to the current affective state., Conclusions: Our results shed new light on the clinical phenotypes of BD, suggesting that timing might be used as a model system of the ongoing pathophysiological process., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Alterations in hippocampal structure and function are present in bipolar disorder (BD). Childhood trauma is associated with risk for BD, and the several subfields of the hippocampus are differentially sensitive to the effects of stressors of the sort associated with risk for BD. The current study therefore sought to test the hypothesis that childhood trauma may be differentially associated with abnormal hippocampal subfield volumes in BD., Methods: 104 participants with BD type I (BD-I, n = 56) or BD type II (BD-II, n = 48) and 81 healthy controls (HC) underwent high-resolution structural magnetic resonance neuroimaging. Hippocampal subfield volumes were determined using FreeSurfer. Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ)., Results: There were significant effects of diagnosis on intracranial volume corrected hippocampal subfield volumes bilaterally as well as a significant interaction between diagnosis and childhood trauma. Hippocampal volumes did not differ between the BD-I and BD-II subgroups but hippocampal volumes were smaller in both groups when compared to HC. There was a significant effect of childhood trauma on bilateral presubiculum volume as well as significant interactions between diagnosis and childhood trauma on bilateral CA1, presubiculum and subiculum volumes, the direction of which differed between individuals with BD (larger) and HC (smaller)., Limitations: Recall bias may influence the reliability of the retrospective assessment of childhood trauma experiences., Conclusions: Childhood trauma demonstrates differential effects on hippocampal subfield volumes of BD and HC, particularly in hippocampal subfields involved in emotion regulation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Prior studies on the effects of lithium on limbic and subcortical gray matter volumes are mixed. It is possible that discrepant findings may be explained by the duration of lithium exposure. We investigated this issue in individuals with type I bipolar disorder (BP-I)., Methods: Limbic and subcortical gray matter volume was measured using FreeSurfer in 60 subjects: 15 with BP-I without prior lithium exposure [no-exposure group (NE)]; 15 with BP-I and lithium exposure < 24 months [short-exposure group (SE)]; 15 with BP-I and lithium exposure > 24 months [long-exposure group (LE)]; and 15 healthy controls (HC)., Results: No differences in limbic and subcortical gray matter volumes were found between LE and HC. Hippocampal and amygdalar volumes were larger bilaterally in both LE and HC when compared to NE. Amygdalar volumes were larger bilaterally in SE when compared to NE but did not differ from LE. Hippocampal volumes were smaller bilaterally in SE when compared to LE and HC but did not differ from NE. No between-group differences on subcortical gray matter or other limbic structure volumes were observed., Limitations: Cross-sectional design and concurrent treatment with other medications limit attribution of between-group differences to lithium exposure alone., Conclusions: The effect of lithium exposure on limbic and subcortical gray matter volumes appears to be time-dependent and relatively specific to the hippocampus and the amygdala, with short-term effects on the amygdala and long-term effects on both structures. These results support the clinical importance of long-term lithium treatment in BP-I., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Diffusion tensor imaging (DTI) studies of bipolar disorder (BD) report contrasting results and are mainly focused on bipolar I (BD-I) samples. We aimed at investigating how and where DTI parameters differ between BD-I and bipolar II (BD-II) and between BD and healthy control subjects (HC)., Methods: We conducted a tract-based spatial statistics analysis of DTI derived parameters, namely fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) in a matched sample of 50 BD (25 BD-I and 25 BD-II) during the chronic course of the illness and 50 HC., Results: Compared to BD-I and HC, BD-II showed lower FA but no significant AD or RD differences in the right inferior longitudinal fasciculus (ILF). Both patient groups showed lower AD and RD in the left internal capsule and lower AD across the left ILF, the cortico-spinal tract within the right hemisphere and bilaterally in the cerebellum with respect to HC., Limitations: Patients were medicated at the time of scanning; the BD-II group had higher Hamilton Rating Scale for Depression scores than the BD-I group., Conclusions: BD-II patients differ from BD-I in the ILF. Both BD subtypes showed widespread white matter (WM) changes in the internal capsule, cortico-spinal tract and cerebellum. The loss of WM integrity in BD-II might be due to demyelination whereas WM changes common to both subgroups could be attributable to axonal damage., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Several neuroimaging studies report reduced hippocampal volume in depressed patients. However, it is still unclear if hippocampal changes in healthy individuals can be considered a risk factor for progression to clinical depression. Here, we investigated subclinical depression and its hippocampal correlates in a non-clinical sample of healthy individuals, with particular regard to gender differences., Methods: One-hundred-two participants underwent a comprehensive clinical assessment, a high-resolution T1-weighted magnetic resonance imaging and diffusion tensor imaging protocol using a 3T MRI scanner. Data of macro-(volume) and micro-(mean diffusivity, MD) structural changes of the hippocampus were analyzed with reference to the Beck Depression Inventory score., Results: Results of multivariate regression analyses revealed reduced bilateral volume, along with increased bilateral MD in hippocampal formation predicting subclinical depressive phenomenology only in healthy males. Conversely, subclinical depressive phenomenology in healthy female was accounted for by only lower educational level, in the absence of any hippocampal structure variations., Limitations: To date, this is the only evidence reporting a relationship between subclinical depressive phenomenology and changes in hippocampal formation in healthy individuals., Conclusions: Our findings demonstrated that reduced volume, along with increased MD in hippocampal formation, is significantly associated with subclinical depressive phenomenology in healthy males. This encourages to study the hypothesis that early macro- and microstructural changes in hippocampi associated with subclinical depression may constitute a risk factor of developing depressive disorders in males., (© 2013 Elsevier B.V. All rights reserved.)